Increased attention has been drawn to the recreational use and abuse of prescription pharmaceutical compositions. The abuse, or non-medicinal use, of prescription pharmaceutical compositions is an increasing problem. Accordingly, preventing the abuse of prescription pharmaceuticals through the development of abuse deterrent pharmaceutical compositions has become a high public health priority for the U.S. Food and Drug Administration (FDA). Prescription pharmaceutical compositions that are typically misused or abused fall, primarily, into three groups: (1) opioids prescribed for pain; (2) Central Nervous System (CNS) depressants prescribed for anxiety or sleep problems; and (3) stimulants, prescribed, for example, for attention deficit hyperactivity, narcolepsy, or obesity.
Methods for abusing prescription pharmaceutical compositions are varied and can include, for example, extraction, boiling, melting, volatilization, physical tampering (e.g., grinding, grating, crushing, etc.), or direct administration. For purposes of abuse, methods of administering active drug substances obtained from prescription pharmaceutical compositions or of the pharmaceutical compositions themselves are similarly diverse and include, for example, injection, smoking, snorting, swallowing, sublingual or buccal administration, chewing, or administration as an anal or vaginal suppository. Alcohol-induced “dose dumping,” i.e., the rapid release of active pharmaceutical ingredients in the presence of a solvent such as ethanol, is also an abuse concern and safety issue. Other methods include rapid extraction under aqueous boiling conditions.
Many pharmaceutical formulations have an immediate “burst release” or “bolus release” of the API as the surface of the dosage from begins to rapidly dissolve. The high burst release of abuse-prone active ingredients contributes to the addictive “pleasant high” or “euphoric” effect and can also result in potentially dangerous blood plasma levels of the API (e.g., Cmax) that can potentially be toxic. The burst release of active ingredients is particularly evident for monolithic controlled release drug platforms. The toxicities associated with abuse-prone drugs can be drastically increased when multiple dosages are taken simultaneously and can result in overdosing or death.
There are a number of strategies for preventing the abuse of pharmaceuticals. Physical and chemical barriers can prevent or hinder extraction of the drug or change the form of the drug making it less likely to be abused. Combinations of agonists and antagonists can be used, wherein the antagonist is only released upon product manipulation or tampering. Another strategy is to use aversive compounds that produce an unpleasant effect when the dosage form is tampered and compromized. In addition, prodrugs can be used, which are only changed into the active form of the drug in the gastrointestinal tract. The pharmaceutical industry is utilizing these strategies to develop abuse-deterrent pharmaceutical compositions in order to reduce the potential for misuse of prescription pharmaceutical compositions.
There remains a need for new abuse deterrent pharmaceutical compositions that have enhanced controlled release properties and prevent the burst release of the active pharmaceutical ingredient.